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Corona pandemic - how does it work? - how to cope?

1. What is the sudden origin of sars-cov2?
2. How do we get infected?
3. Why are there ever more dangerous variants?
4. Is there hope for medical treatment of infections?
5. Will vaccination conquer the virus?
6. What should I do?

1. What is the sudden origin of sars-cov2?
Corona viruses are abundant, they infect a variety of organisms. Among the > 1500 human pathogenic viruses there are a handful of corona variants, mainly causing a kind of cold. Our immune system is mostly successful against viruses, but sometimes the bugs are faster and invade our cells before elimination.
The genome of RNA-viruses is less stable compared to our genome; the rate of mistakes in passing the genetic information to offspring is about 10 000 fold higher than our's (ca. 10^-5 to ca. 10^-9). Thus, there originate (accidentially) also mutants with an advantage in the race against our immune system. Such mutants will spread faster in the environment.
Next kin to the currant cov2 is a virus found in bats, cov1 of 2003 is genetically less related. The bat virus mutated in a way to be able to infect us (some people discuss a little help by investigators in a chinese military research institution funded by the USA).

2. How do we get infected?
Viruses as such are dead matter, they have no metabolism at all. To multiply they need host cells, whose metabolism they usurp. To enter a cell, they first have to attach firmly to a receptor (that is a defined structure at the surface of the host cell). Usage of the host cell's metabolism may damage the cell so it dies.

From the membrane of cov2 protude protein structures called spikes, as seen in an artist's view above. The knobby ends of the spikes bind to the receptor, which in mammals is the enzyme angiotensin converting enzyme 2 (ACE2, used all over our body to regulate blood pressure). The real (molecular) shape of the spikes is demonstrated here. In contrast to the artistic view the spikes are bound in a flexible manner to the viral surface, which aides in the docking efficiency.

3. Why are there ever more dangerous variants?
A corona variant will be dangerous when binding of the spike to the receptor is so strong that an untrained immune system is unable to compete with the binding. Training of the immune system is brought about by vaccination or survival of an infection. The evolutionary way of corona viruses is shown here.

Corona viruses mutate forever. Since the 2019 Wuhan strain there are unnumbered further mutants, some of which make it into the headlines. Mutations in the spikes are distributed all over the protein.
November 2021: From alpha to omega - what does it mean? The World Health Organization classifies corona variants according to health threats in variants of interest or variants of concern. Here is the classification according to mutations in the spike protein (the picture below is from the WHO website; in the literature you find more/other mutations in the delta variant):

The omicron data are from https://github.com/cov-lineages/pango-designation/issues/343 and https://github.com/cov-lineages/pango-designation/issues/361.
The positions of the individual amino acid changes are demonstrated via the structure of the delta variant.
A vaccine directed against the original Wuhan corona strain may have severe difficulties to protect against heavily mutatet variants (there are more mutations in other viral proteins). Instead of promising a less severe course of illness by vaccinating with a drug directed to a virus extinct since two years it might be better to develop something efficient against current versions of the virus, asap. For remaining vaccination protection s. below.

4. Medical treatment
Swallow a sweet pill at the first itching in the throat and corona byebye - a nice prospect, but we will have to wait for that until the pandemic is over.
But seriusly, what may be possible to stop the viruses multiplying in our body? We have to look for specialities in the viral metabolism which don't occur in our body and thus allow a selective poisoning of the virus.

• The chemical base of the genome of corona viruses is single stranded RNA (our genome is governed by double stranded DNA). Mammalian metabolism provides no means to multiply sigle stranded RNA, so the sRNA-viruses have to care for their own RNA polymerase. Research on this level is ongoing for years, for there are other nasty RNA viruses like HIV or Ebola. What is effective against one virus is not neccessarily against another, for each virus has its own evolutionary way (however the basic function of all RNA polymerases is the same).

• Let's first have a look at the mechanism of the RNA polymerase of cov2. The anti-viral remdesivir diminishes the activity of the RNA polymerase, it was used to treat ebola infections. Because of severe side-effects remdesivir has to be administered by a strict protocol to prevent even greater damage to sars patients. Here the blocking of the RNA polymerase by remdesivir is shown.

• Another speciality is the viral protein synthesis. In our body each protein is produced on its own with an elaborate regulation mechanism according the actual demand. That is quite an effort, but it is neccessary to adopt to changing demands according to living circumstances. That doesn't concern corona viruses: their pattern to express all 16 non structural proteins is fixed without any regulation involved. So these proteins are produced in one run without interruption. Later this superprotein is cut into the demanded pieces. That requires a very special protease which exactly knows where to cut. This protease is provided by the viruses. Being a special enzyme, it offers the opportunity for special inhibitors. People infected with hepatitis c (HCV) or HIV were successfully treated with boceprevir; in cell cultures also multiplication of cov2 was blocked. To my knowledge no clinical studies with human covid-19 infections were published so far. Structural investigations revealed the efficiency against cov2 protease.

• Antibody & Co: in our body the natural weapon against infections are antibodies, produced by our immune system. A cov2 infection will provoke a bunch of antibodies against different viral components. From the blood of corona survivors you may isolate these antibodies, their administration is the last hope for doomed patients. The former president of the USA believed after treatment with antibodies that sars-viruses are harmless. So what. The industrial production of antibodies is limited to only one type each (monoclonal antibodies, mAB) because of procedural limitations. For human treatment a mixture of different mAB is more suitable in view of (unknown) variants of the virus. The working of an efficient antibody is shown here.
Complete antibodies (as produced by our immune system) are sensitive molecules. Production is complicated and medical administration quite expensive. A suspension has to be injected intravenously providing protection for a short time only - so for extreme situations only. But the principle is of genius: tailor-made molecules block vital functions of the viruses. Is it possible to mimic this with stable substances? Like a preventive nasal spray agains corona? There is hope, offered by nature itself: camel-like animals produce antibodies of a much simpler kind, however as efficient as human types. Researchers infected alpacas with cov2 and gained from ther blood antibodies, which were processed to neutralizing nanobodies. These may be produced with the help of bacteria, like human insulin for the treatment of diabetes. A neutralizing nanobody is shown here fighting against corona. Nanobodies didn't make it yet to the pharmacists, research in this field beeing rather young.

• There is a catch in the development of substances against RNA viruses. Anything will work as long as there are no viral escape mutants. As soon as the viral target is unrecognizable to chemical substance or antibody, you may start to develop anew. So human target structures may be better candidates for preventive or therapeutic strategies. A group of researchers investigated the interactions between viral and human proteins on a global scale.
In another study researchers developed an ACE2 decoy to prevent spike docking to the real target.
December 2021: based on the decoy a medicine (Ensovibep, https://doi.org/10.1101/2021.02.03.429164) was developed and is ready for use.

• If the NHS is reluctant to help, is there any home remedy? With a mild corona infection there is - like with any cold. Untreated it lasts a week, treated just 7 days. But you may feel better. There are people favoring traditional chinese medicine. The Bavaria-based SMS (societas medicinale sinensis) headquarters offer via https://www.tcm.edu help in all situations regarding the human body (including corona infections). I am not aware of a British branch of that society.
September 2022: Tradition meets modern times - databanks and supercomputing find active ingredients in traditionally used herbs. A study on licorice predicts research results.

5. Vaccination
As long as there is no efficient yet simple treatment for covid-19 soon to be expected, the only prophylaxis is vaccination. To develop a vaccine agains cov2 you have to know the biology of the spikes. Here the biochemistry of the spike development is shown.
There is not only a medical aspect of vaccination. So vaccine producers are a bit tight about publishing details of their products. Novavax doesn't use mRNA or DNA carried by a (harmless?) helper virus, but produces whole modified spike trimers to vaccinate. The structure of the vaccine spikes was published. In april 2021 also BioNTech & Co published structural data about their mRNA-vaccine coded spike protein bound to ACE2 (https://doi.org/10.1038/s41586-021-03275-y). As with Novavax the development is based on the Wuhan strain of the virus.

December 2021: newest publications allow to estimate properties of the omicron variant of the corona virus. Effects to the immune protection by now outdated vaccines are severe. Have a look at an omicron summary. Preliminary reults (https://doi.org/10.1101/2021.12.14.21267755) indicate the necessity for a booster shot of current vaccines every two to three months. How in the eyes of uncle Scrooge the $ signs will shine!

January 2022: Structure data for the omicron variety are released - data for binding to the ACE2 receptor and the efficiency of antibodies are shown.

September 2022: mRNA-Vaccine producers responded to the urgent need to protect against omicron infections. Science (https://www.science.org/content/article/omicron-booster-shots-are-coming-lots-questions) summarizes the current state of affairs as to effectiveness and availibility.

The picture shows amino acid changes in the spike protein for a region, where neutralizing antibodies bind to prevent an infection.

October 2022: BioNTech/Pfizer offer a booster vaccine with a mixture of Wuhan und BA.5 spike-mRNA.
6. Every man for himself!
We catch a corona infection only when viruses enter our body. And if we have no immune protection. So, as long as your vaccination immune protection is not complete (implying you belong to the happy 90% where vaccination is successful) you should avoid breathing contaminated aerosols or get into contact with bodily excretions of possibly infected organisms (bats, men, zoo-animals, mammalian pets). This provokes conflicts for the working part of the population and psychic problems for people in isolation. Nevertheless: keep distance! Viruses are too tiny to be seen by the naked eye in your surroundings.

15-7-2021  /  Rolf Bergmann  /  http://www.papanatur.de/jsmol/coronaE.html